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John M. Abrahams, Maria Torchia, Mary Putt, Larry R. Kaiser and Kevin D. Judy

Object. The authors present their experience with the treatment of brain metastases from non—small cell lung carcinoma (NSCLC).

Methods. A retrospective review was conducted in which records from 74 patients treated at the authors' institution between 1994 and 1999 were assessed. Survival and functional outcome were reviewed relative to individual patient variables. The median survival time was 12.9 months, with 1-, 2-, and 5-year survival milestones reached by 52.2%, 30.7%, and 18.1% of patients, respectively. Patients were stratified into groups composed of those with synchronous brain metastases (tumors diagnosed within 3 months of NSCLC) and metachronous brain metastases (tumors diagnosed 3 months after NSCLC). The median survival time and 5-year survival rate were 18 months and 28.9% for metachronous, compared with 9.9 months and 0% for synchronous brain metastases. In univariate analyses, the stage of brain metastases, an initial Karnofsky Performance Scale (KPS) score of 90 or less, and conservative therapy for NSCLC were associated with worse outcomes (p < 0.05). In analyses in which tumors were stratified by synchronous compared with metachronous brain metastases, a preoperative KPS score of 90 or less and radiation therapy (RT) alone for brain metastases were associated with worse outcomes in patients with metachronous brain metastases but not with synchronous tumors (p < 0.05). When stratified by preoperative KPS score, the synchronous brain metastases stage or treatment of brain metastases with RT alone were associated with worse outcome in patients with KPS scores of 100, but had no discernible effect on patients with KPS scores of 90 or less (p < 0.05).

Conclusions. The tumor stage and preoperative KPS score were significantly associated with survival. Craniotomy plus RT significantly improved the prognosis in patients with metachronous brain metastases or those with a preoperative KPS score of 100.

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Kevin D. Judy, Alessandro Olivi, Kwame G. Buahin, Abraham Domb, Jonathan I. Epstein, O. Michael Colvin and Henry Brem

✓ Most malignant gliomas grow despite treatment by standard chemotherapeutic agents. The authors explored the use of an innovative drug, 4-hydroperoxycyclophosphamide (4HC), delivered via a controlled-release biodegradable polymer to determine whether local delivery would enhance efficacy. This drug is an alkylator-type chemotherapeutic agent derived from cyclophosphamide. Unlike the parent drug, which requires activation by hepatic microsomes, 4HC is active in vitro. Two rat glioma cell lines, 9L and F98, were treated in cell culture with medium containing 4HC. Both cell lines were more sensitive to 4HC than to a nitrosourea, BCNU, an agent of established value in the local therapy of gliomas.

Ninety Fischer 344 rats implanted with 9L or F98 gliomas were treated with an intracranial polymer implant containing 0% to 50% loaded 4HC in the polymer, and it was found that 20% 4HC—loaded polymers caused minimum local brain toxicity and maximum survival. These polymers were then used to compare the in vivo efficacy of 4HC to BCNU in rats implanted with 9L glioma. Animals with brain tumors treated with 4HC had a median survival span of 77 days compared to the median survival of 21 days in BCNU-treated animals and median survival of 14 days in untreated animals. Long-term survival for more than 80 days was 40% in the 4HC-treated rats versus 30% in the BCNU-treated rats.

The polymer carrier used in this study was a copolyanhydride of dimer erucic acid and sebacic acid 1:1, which was able to maintain the hydrolytically unstable 4HC in a stable state for local delivery. Thus, it is concluded that 4HC-impregnated polymers provide an effective and safe local treatment for rat glioma.

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Robert G. Whitmore, Jaroslaw Krejza, Gurpreet S. Kapoor, Jason Huse, John H. Woo, Stephanie Bloom, Joanna Lopinto, Ronald L. Wolf, Kevin Judy, Myrna R. Rosenfeld, Jaclyn A. Biegel, Elias R. Melhem and Donald M. O'rourke

Object

Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms.

Methods

Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade.

Results

In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96–3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27–2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59–6.26; four patients) and Group 2 (mean 2.83, range 1.81–3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59–6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96–3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively.

Conclusions

Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.

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Manmeet Ahluwalia, Gene H. Barnett, Di Deng, Stephen B. Tatter, Adrian W. Laxton, Alireza M. Mohammadi, Eric Leuthardt, Roukoz Chamoun, Kevin Judy, Anthony Asher, Marco Essig, Jorg Dietrich and Veronica L. Chiang

In Brief

The outcome of patients undergoing laser ablation for the treatment of brain metastases that had become problematic after stereotactic radiosurgery was prospectively studied. This trial is important because the number of cancer patients undergoing brain radiosurgery is rising exponentially, making this clinical scenario an increasingly likely problem. This study shows the aggregate results that were achieved across multiple centers in the United States.